Cardiovascular disease (CVD) remains the most common cause of death in the US. CVD currently claims nearly one million lives yearly in the U.S., accounting for nearly 40% of all deaths. The total cost of CVD in the U.S., including hospitalizations and lost productivity, is approximately $300 billion annually. Coronary artery disease (CAD) accounts for the largest number of deaths and the majority of these costs. While the efforts aimed at treating this disease in recent decades have concentrated on surgical and catheter-based interventions, limited resources have been directed toward prevention and rehabilitation. Over the last decade, the use of percutaneous coronary intervention (PCI) has increased exponentially. Between 1996 and 2007, the number of PCIs performed in the U.S. increased more than 4-fold, from approximately 300,000 to more than 1.3 million yearly. During this time, PCI has accounted for 10% of the overall increase in Medicare expenditures. In light of the extraordinary increase in the use of this technology in recent years, questions have been raised regarding the cost-effectiveness of PCI, the extent to which PCI is overused, and whether selected patients may benefit from optimal medical therapy in lieu of PCI. Despite the fact that PCI is expensive, repeat PCI is common and there is no evidence for improved survival, alternative therapies are rarely considered. One alternative therapy that has been shown to improve outcomes in PCI candidates is exercise training. In the PCI vs. Exercise Training (Leipzig) study, PCI candidates randomized to one year of exercise training had improved coronary anatomy, higher exercise capacity, an improvement in quality of life and event-free survival, as well as lower health care costs when compared to the PCI group. However, the Leipzig study employed invasive angiographic methods which do not provide information on dynamic coronary flow or atherosclerosis specifically, and do not provide insight into the mechanism of atherosclerosis progression or regression. In addition, economic analyses were limited to cost per change in Canadian Cardiovascular Society Class; the Leipzig study did not assess cost effectiveness. Given the high volume of PCI, its high cost, its lack of effect on survival and the potential for alternative treatments including exercise and risk reduction in PCI candidates, the current proposal is termed PCI Alternative Using Sustained Exercise (PAUSE). The primary aim of PAUSE is apply newer imaging technologies to determine whether patients randomized to an exercise program have greater improvement in coronary function and anatomy compared to those randomized to PCI. Both groups will receive optimal medical management. We will also compare health care costs, symptoms, quality of life, and clinical outcomes between the two groups. At baseline and one year after randomization, patients will undergo an assessment of physical activity patterns and fitness using standardized questionnaires and maximal cardiopulmonary exercise testing (CPX). Patients will also undergo a detailed evaluation of coronary function and anatomy with positron emission tomography combined with computed tomographic angiography (PET/CTA). PET will be used to measure myocardial perfusion and endothelial function. CTA will be used to evaluate anatomical progression of atherosclerotic disease based on a qualitative scoring system and quantitative measurement of calcified and noncalcified plaque burden. The combination of PET/CTA provides information that previously could only be obtained invasively using coronary flow wires and invasive x-ray angiography. This will permit a noninvasive way to evaluate both functional and anatomical adaptations to exercise. Our overall objective is to demonstrate the utility of a non-invasive technology to document the efficacy of exercise as an alternative treatment strategy to PCI for coronary lesions.